The proposed research is aimed at achieving a better understanding of the basic cellular mechanisms of bile acid, organic anion and inorganic anion transport by the hepatocyte. Such knowledge will hopefully lead to further insights into the function of the liver both in health and during bile secretory failure (cholestasis). The proposal is divided into four areas of investigation. The first and largest area involves transport studies in rat liver plasma membrane vesicles and will deal with the driving forces, determinants, regulation, and inhibition of bile acid uptake across the basolateral membrane. Similar studies of the uptake of the organic anion sulfobromophthalein will be performed. Basolateral membranes will be prepared by a new technique. The second area of investigation will examine the relationship between active ion transport and oxygen consumption in isolated rat hepatocytes. Third, electron microscopic autoradiographic studies of bile acid transport will be performed in the isolated perfused rat liver with l25I-cholylglycylhistamine as a probe of possible vectorial transport. Finally, we will study the effects of adrenergic agents on the bile acid uptake process and on the sodium pump.